David H. Strauss

Antibodies to the human 60 kDa heat-shock protein in patients with schizophrenia

Immune mechanisms are thought to be important in a subpopulation of patients with schizophrenia. We examined the specificity of neural antibodies in patients with schizophrenia to identify a possible antigen. Serum antibodies from patients with schizophrenia and control subjects were tested for binding to protein extracts of human neuroblastoma cells by western blot. Protein antigens were characterised by aminoterminal and internal aminoacid sequence analysis. 14 of 32 (44%) otherwise healthy patients with schizophrenia had antibodies to a neuroblastoma protein of molecular weight 60 kDa. By partial sequence analysis, this protein was identified as the 60 kDa human heat-shock protein (hsp) that is the P1 mitochondrial protein, and which is 50% homologous to the mycobacterial 65 kDa hsp. Antigens that crossreact with hsp65 have been implicated in the pathogenesis of adjuvant-induced arthritis in rats and autoimmune diabetes in mice. Of 100 normal subjects or disease controls, antibodies to hsp60 were found in only 8 patients, all of whom had active infectious or inflammatory disease. Our results support the presence of abnormal immune reactivity involving hsp60 in a subset of patients with schizophrenia. The immune response may be related to the pathogenesis of the disease.

Psychobiological heterogeneity of familial and sporadic schizophrenia

BACKGROUND Although schizophrenia is presumed to be heterogeneous, there has been limited success distinguishing familial from sporadic cases. We used psychobiological measures to examine heterogeneity, as they may be closer to neurobiology than symptoms. Smooth pursuit eye movement quality (SPEM) and dichotic listening (DL) tests to tones and words were used to assess hemispheric laterality asymmetry. METHODS Forty-six research unit patients participated in assessments of family history (FH) and physiological measures. FH was categorized by three exclusive groups: FH-1 patients had a chronic schizophrenia-related psychosis in a first-degree relative, FH-2 had it in second-degree relative, and FH-3 had no family member with a reoccurrence. RESULTS Analysis of variance showed a significant group difference for SPEM and DL tones. SPEM was significantly worse in all three schizophrenia groups than for the normal comparison subjects. Among the schizophrenia groups, the nonfamilial group (FH-3) had the worst SPEM quality, FH-2 had intermediate quality, and FH-1 had the best quality. Conversely, only the nonfamilials (FH-3) had normal right hemispheric lateralization for tones, whereas familials did not, and FH-2 again had intermediate values. The lateralization quotient for DL words did not significantly differ among the groups. CONCLUSIONS SPEM was affected most in sporadic, not familial schizophrenia, whereas dichotic listening was most affected in familial schizophrenia. This double dissociation supports the utility of the familial/sporadic distinction and suggests that etiological factors in different forms of schizophrenia may impact principally on distinct neurobiological substrates, despite similar patient phenomenology.

Elevation of CD5+ B lymphocytes in schizophrenia.

BACKGROUND A variety of immunologic alterations have been observed in patients with schizophrenia. These findings have lent support to theories that autoimmune mechanisms may be important in some patients with the illness. The CD5+ B lymphocyte, a B-cell subset associated with autoimmune disease, has been the subject of two previously published studies yielding disparate results. METHODS In this study, we used immunofluorescent flow cytometry to measure CD5+ B cells, total B and T cells, and CD4 and CD8 subsets in patients with schizophrenia and in normal control subjects. RESULTS A significantly higher percentage of patients with schizophrenia, relative to normal control subjects, exhibited an elevated level of CD5+ B cells (27.6% vs 6.7%). Antipsychotic withdrawal had no effect on CD5+ B-cell levels, suggesting that medication effects were not the cause of this difference. No other studied lymphocyte subsets differed between the two groups. CONCLUSIONS A subset of patients with schizophrenia have elevated levels of CD5+ B cells. This finding replicates an earlier study by another group and provides further evidence suggestive of autoimmune manifestations in schizophrenia.

Variability in the definition and reporting of adverse events in suicide prevention trials: an examination of the issues and a proposed solution.

Adverse events (AEs) and serious adverse events (SAEs) are important outcomes of any intervention study yet are under-researched. Vague and variable definitions and substantial underreporting make comparisons of risk between studies difficult and evaluation of the safety of a particular intervention almost impossible. These realities may deter researchers from studying at-risk populations. Suicidal behavior is an adverse event in any study, and potentially a very serious one. Thus the issues of reporting and definition are particularly salient for researchers who work with populations at risk for suicidal behavior, especially when the suicidal behavior is the outcome of interest. We conducted a qualitative study with experienced suicide researchers and intervention experts to delineate the issues related to reporting serious adverse events faced by investigators conducting trials in suicide prevention. Participants from multiple sites were interviewed by phone, interviews transcribed and coded for definition and reporting issues and suggested solutions. A narrative synthesis was prepared and validated by all participants. Participants highlighted the difficulties in defining AEs and SAEs and stressed the importance and complexity of ensuring the AE was related to the study and reported properly, and were in agreement about the consequences of AEs to both institutions and individuals. Participants identified the need for the development of clear and consistent AE definitions and reporting requirements. Clear and consistently applied definitions of adverse and serious adverse events and reporting requirements would enhance the comparability of intervention studies in suicidal populations.

Participation in HIV Behavioral Research: Unanticipated Benefits and Burdens

HIV behavioral research has provided an invaluable knowledge base for effective approaches to behavioral challenges along the HIV care cascade. Little attention has been paid to tracking unanticipated effects of research participation, whether negative or positive. We used qualitative methods to elicit impressions of unanticipated effects of participation in behavioral research. An instrument was developed and piloted to assess positive (emotional gains, practical gains, HIV prevention knowledge and skills gains) and negative (emotional stress, discomfort with research) unanticipated effects. Participants (N = 25) from five projects, including men who have sex with men, adults who use substances, and youth, reported multiple positive unanticipated effects (sexual and drug risk reduction, goal setting, improvements in self-esteem and mood, relationship gains, health care behavior gains, knowledge and introspection gains) and rare unanticipated negative effects. Developing a systematic tool of unanticipated positive and negative effects of participation in behavioral research is a crucial next step.ResumenLa investigación sobre comportamientos relativos al VIH ha proporcionado una base de conocimientos invalorables para lidiar efectivamente con los desafíos por conductas a lo largo de la cascada de atención por el VIH. Poca atención ha sido prestada en documentar los efectos imprevistos de la participación en investigación, ya sean negativos o positivos. Utilizamos métodos cualitativos para obtener impresiones de los efectos imprevistos de la participación en la investigación conductual. Se desarrolló y se aplicó un instrumento para evaluar los efectos positivos (ganancias emocionales, ganancias prácticas, conocimientos y ganancias de la prevención del VIH) y negativos (estrés emocional, incomodidad con la investigación). Los participantes (N = 25) de cinco proyectos, incluyendo hombres que tienen sexo con hombres, adultos que usan sustancias, y jóvenes, informaron múltiples efectos positivos no previamente anticipados (reducción del riesgo sexual y de drogas, establecimiento de metas, mejoras en la autoestima y el estado de ánimo, mejoras en relaciones personales, mejoras en buscar atención médica, ganancias de conocimiento e introspección) y raramente efectos negativos no anticipados. Desarrollar una herramienta sistemática para evaluar efectos positivos y negativos no anticipados de la participación en la investigación conductual es el paso crucial próximo.

Research cuts threaten public trust

In her News In Depth story “NIH overhead plan draws fire” (2 June, p. [893][1]), J. Kaiser reports that President Trumps budget proposal cuts the National Institutes of Health budget by

Awareness of Illness in Schizophrenia and Schizoaffective and Mood Disorders

4.6 billion without affecting spending on science by substantially reducing payments for indirect costs.